Potassium channels are membrane-spanning proteins that generally act to hyperpolarize neurons. Physiological studies indicate that potassium currents are found in most cells and are associated with a wide range of functions, including the regulation of the electrical properties of excitable cells. Depending on the type of potassium channel, its functional activity can be controlled by transmembrane voltage, different ligands, protein phosphorylation, or other second messengers.
In the last decade, the cloning of potassium channels has resulted in the discovery of the molecular isolation and characterization of greater than 50 potassium channel genes and many of their associated regulatory subunits. More recently, a new family of potassium channel genes, the KCNQ gene family, has been described (N. A. Singh et al., 1998, Nature Genet., 18:25-29; C. Charlier et al., 1998, Nature Genet., 18:53-55; C. Biervert et al., 1998, Science, 279:403-406). The KCNQ family of potassium channels are voltage dependent potassium channels. They contain the voltage sensor and pore signature sequences characteristic of a 6 transmembrane potassium channel gene and have a longer carboxy-terminus than other known voltage-dependent potassium channels.
A remarkable aspect about the KCNQ1-4 gene family is that mutations in each channel are associated with a particular disease, including cardiac arrhythmias (KCNQ1), epilepsy (KCNQ2 and KCNQ3), and hearing loss (KCNQ4). The present invention provides a newly isolated, cloned and characterized member of the KCNQ family, called KCNQ5. Human KCNQ5 provides the art with an additional member of the KCNQ family of potassium channel proteins, isolated from a human source, for use in the methods and compositions described herein.